This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The NOS family is a key target for development of new pharmaceuticals for a wide range of diseases that currently lack effective treatments including stroke, septic shock, hypertension and cancer. However, due to an incomplete understanding of the molecular mechanisms of NOS regulation, NOS inhibitors have not yet been available for clinical treatments. The proposed studies will significantly improve the fundamental understanding of NOS regulation, and has the potential of facilitating bio-rational development of new selective mechanism-based drug entities to target these clinically important NOS isoforms.